We propose to purchase a Zeiss EM 902 transmission electron microscope with Castaing energy filter, to replace a worn-out JEOL JEM100B-3 that has been serving the day-to-day needs of the faculty of the Biophysics Research Division and the Great Lakes Research Division of The University of Michigan. The existing microscope has been inoperable during half of 1985, causing discontinuation of at least one research project and the performance of other projects off-site. The new instrument will be used for routine microscopy of crystals of soluble proteins, DNA, and isolated sea urchine histone gene chromatin. Low dose microscopy of glucose-embedded and frozen-hydrated periodic arrays of membrane-bound proteins are also planned. Advanced microscopy of negatively-stained and of frozen-hydrated chromatin will be used to directly test and refine a recently proposed model for the internal structure of chromosome fibers. Greater contrast will be achieved by elimination of the inelastic electrons, which dominate the images of frozen molecules. Electron spectroscopic imaging will be used to determine the radial distribution of protein and DNA in chromatin fibers. In addition, inelastic dark field microscopy will be developed for quantitative mass analysis of unstained biological molecules -- a unique application supported by two faculty who have productively used the scanning transmission electron microscopy facilities at Brookhaven National Laboratory to determine the distribution of mass within chromosome fibers and enzymes. The microscope will be located in the Biophysics Research Division of The University of Michigan, which will assure that its unique capabilities will be fully exploited for biochemical, biophysical, and cell biological studies at the molecular level.